1887

Abstract

The UL41 gene product (vhs) of herpes simplex virus (HSV) is packaged in the virion, and mediates host protein synthesis shutoff at the early stage of the virus replication cycle. In order to clarify the role of vhs in virus replication and virulence, we isolated a completely UL41-deficient mutant (the VRΔ41 strain) and its revertant (the VRΔ41R strain). In the mouse encephalitis model, the replication of strain VRΔ41 was inhibited after 2 days post-infection, resulting in low virulence, by γ-ray-sensitive cells such as lymphocytes and/or neutrophils. The result suggested that some cytokines, produced in VRΔ41-inoculated brains, activate and induce the migration of γ-ray-sensitive cells to the infection site. Therefore, cytokines produced by HSV-1-infected human cells were screened, and potent inductions of interleukin (IL)-1β, IL-8 and macrophage inflammatory protein-1α by VRΔ41 infection were observed. Moreover, the VRΔ41 strain showed 20- and 5-fold higher sensitivity to interferon-α and -β compared to the wild-type strain, respectively. These results indicate that one important role of vhs is evasion from non-specific host defence mechanisms during primary infection through suppression of cytokine production in HSV-infected cells and reduction of the anti-HSV activity of interferon-α and -β.

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2000-07-01
2019-12-15
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References

  1. Ahn, K., Meyer, T. H., Uebel, S., Sempé, P., Djaballah, H., Yang, Y., Peterson, P. A., Früh, K. & Tampé, R. ( 1996; ). Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus protein ICP47. EMBO Journal 15, 3247-3255.
    [Google Scholar]
  2. Baggiolini, M., Loetscher, P. & Moser, B. ( 1995; ). Interleukin-8 and the chemokine family. International Journal of Immunopharmacology 17, 103-108.[CrossRef]
    [Google Scholar]
  3. Becker, Y., Tavor, E., Asher, Y., Berkowitz, C. & Moyal, M. ( 1993; ). Effect of herpes simplex virus type 1 UL41 gene on the stability of mRNA from the cellular genes: β-actin, fibronectin, glucose transporter-1, and docking protein, and on virus intraperitoneal pathogenicity to newborn mice. Virus Genes 7, 133-143.[CrossRef]
    [Google Scholar]
  4. Cantin, E. M., Hinton, D. R., Chen, J. & Openshaw, H. ( 1995; ). Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1. Journal of Virology 69, 4898-4905.
    [Google Scholar]
  5. Daikoku, T., Shibata, S., Goshima, F., Oshima, S., Tsurumi, T., Yamada, H., Yamashita, Y. & Nishiyama, Y. ( 1997; ). Purification and characterization of the protein kinase encoded by the UL13 gene of herpes simplex virus type 2. Virology 235, 82-93.[CrossRef]
    [Google Scholar]
  6. Dolan, A., Jamieson, F. E., Cunningham, C., Barnett, B. C. & McGeoch, D. J. ( 1998; ). The genome sequence of herpes simplex virus type 2. Journal of Virology 72, 2010-2021.
    [Google Scholar]
  7. Fabrikant, J. I. (1972). Radiobiology. Chicago: Year Book Medical Publishers.
  8. Fenwick, M. L. & Walker, M. J. ( 1978; ). Suppression of the synthesis of cellular macromolecules by herpes simplex virus. Journal of General Virology 41, 37-51.[CrossRef]
    [Google Scholar]
  9. Frank, I. & Friedman, H. M. ( 1989; ). A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G. Journal of Virology 63, 4479-4488.
    [Google Scholar]
  10. Friedman, H. M., Cohen, G. H., Eisenberg, R. J., Seidel, C. A. & Cines, D. B. ( 1984; ). Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells. Nature 309, 633-635.[CrossRef]
    [Google Scholar]
  11. Früh, K., Ahn, K., Djaballah, H., Sempé, P., Van Endert, P. M., Tampé, R., Peterson, P. A. & Yang, Y. ( 1995; ). A viral inhibitor of peptide transporters for antigen presentation. Nature 375, 415-418.[CrossRef]
    [Google Scholar]
  12. Gidlund, M., Örn, A., Pattengale, P. K., Jansson, M., Wigzell, H. & Nilsson, K. ( 1981; ). Natural killer cells kill tumor cells at a given stage of differentiation. Nature 292, 848-850.[CrossRef]
    [Google Scholar]
  13. Harada, A., Sekido, N., Akahoshi, T., Wada, T., Mukaido, N. & Matsushima, K. ( 1994; ). Essential involvement of interleukin-8 (IL-8) in acute inflammation. Journal of Leukocyte Biology 56, 559-564.
    [Google Scholar]
  14. Hayashi, K., Kurata, T., Morishima, T. & Nassery, T. ( 1980; ). Analysis of the inhibitory effect of peritoneal macrophages on the spread of herpes simplex virus. Infection and Immunity 28, 350-358.
    [Google Scholar]
  15. Hill, A. B., Barnett, B. C., McMichael, A. J. & McGeoch, D. J. ( 1994; ). HLA class I molecules are not transported to the cell surface in cells infected with herpes simplex virus types 1 and 2. Journal of Immunology 152, 2736-2741.
    [Google Scholar]
  16. Johansson, P. J. H., Schröder, A. K., Nardella, F. A., Mannik, M. & Christensen, P. ( 1986; ). Interaction between herpes simplex type 1-induced Fc receptor and human and rabbit immunoglobulin G (IgG) domains. Immunology 58, 251-255.
    [Google Scholar]
  17. Johnson, R. T. ( 1964; ). The pathogenesis of herpes encephalitis. II. A cellular basis for the development of resistance with age. Journal of Experimental Medicine 120, 359-374.[CrossRef]
    [Google Scholar]
  18. Johnson, D. C. & Feenstra, V. ( 1987; ). Identification of a novel herpes simplex virus type 1-induced glycoprotein which complexes with gE and binds immunoglobulin. Journal of Virology 61, 2208-2216.
    [Google Scholar]
  19. Kirchner, H., Engler, H., Schröder, C. H., Zawatzky, R. & Storch, E. ( 1983; ). Herpes simplex virus type 1-induced interferon production and activation of natural killer cells in mice. Journal of General Virology 64, 437-441.[CrossRef]
    [Google Scholar]
  20. Kwong, A. D. & Frenkel, N. ( 1987; ). Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proceedings of the National Academy of Sciences, USA 84, 1926-1930.[CrossRef]
    [Google Scholar]
  21. Kwong, A. D., Kruper, J. A. & Frenkel, N. ( 1988; ). Herpes simplex virus virion host shutoff function. Journal of Virology 62, 912-921.
    [Google Scholar]
  22. Lam, Q., Smibert, C. A., Koop, K. E., Lavery, C., Capone, J. P., Weinheimer, S. P. & Smiley, J. R. ( 1996; ). Herpes simplex virus VP16 rescues viral mRNA from destruction by the virion host shutoff function. EMBO Journal 15, 2575-2581.
    [Google Scholar]
  23. McLauchlan, J., Addison, C., Craigie, M. C. & Rixon, F. J. ( 1992; ). Noninfectious L-particles supply functions which can facilitate infection by HSV. Virology 190, 682-688.[CrossRef]
    [Google Scholar]
  24. McNearney, T. A., Odell, C., Holers, V. M., Spear, P. G. & Atkinson, J. P. ( 1987; ). Herpes simplex virus glycoprotein gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity. Journal of Experimental Medicine 166, 1525-1535.[CrossRef]
    [Google Scholar]
  25. Martin, T. E., Barghusen, S. C., Leser, G. P. & Spear, P. G. ( 1987; ). Redistribution of nuclear ribonucleoprotein antigens during herpes simplex virus infection. Journal of Cell Biology 105, 2069-2082.[CrossRef]
    [Google Scholar]
  26. Nishioka, Y. & Silverstein, S. ( 1977; ). Degradation of cellular mRNA during infection by herpes simplex virus. Proceedings of the National Academy of Sciences, USA 74, 2370-2374.[CrossRef]
    [Google Scholar]
  27. Nishioka, Y. & Silverstein, S. ( 1978; ). Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected with herpes simplex virus type 1. Journal of Virology 27, 619-627.
    [Google Scholar]
  28. Oshima, S., Daikoku, T., Shibata, S., Yamada, H., Goshima, F. & Nishiyama, Y. ( 1998; ). Characterization of the UL16 gene product of herpes simplex virus type 2. Archives of Virology 143, 863-880.[CrossRef]
    [Google Scholar]
  29. Overton, H., McMillan, D., Hope, L. & Wong-kai-in, P. ( 1994; ). Production of host shutoff-defective mutants of herpes simplex virus type 1 by inactivation of the UL13 gene. Virology 202, 97-106.[CrossRef]
    [Google Scholar]
  30. Para, M. F., Baucke, R. & Spear, P. G. ( 1982; ). Glycoprotein gE of herpes simplex virus type 1: effects of anti-gE on virion infectivity and on virus-induced Fc-binding receptors. Journal of Virology 41, 129-136.
    [Google Scholar]
  31. Phelan, A., Carmo-Fonseca, M., McLauchlan, J., Lamond, A. I. & Clements, J. B. ( 1993; ). A herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution. Proceedings of the National Academy of Sciences, USA 90, 9056-9060.[CrossRef]
    [Google Scholar]
  32. Read, G. S. & Frenkel, N. ( 1983; ). Herpes simplex virus mutants defective in the virion-associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of (immediate early) viral polypeptides. Journal of Virology 46, 498-512.
    [Google Scholar]
  33. Read, G. S., Karr, B. M. & Knight, K. ( 1993; ). Isolation of a herpes simplex virus type 1 mutant with a deletion in the virion host shutoff gene and identification of multiple forms of the vhs (UL41) polypeptide. Journal of Virology 67, 7149-7160.
    [Google Scholar]
  34. Roizman, B., Borman, G. S. & Rousta, M.-K. ( 1965; ). Macromolecular synthesis in cells infected with herpes simplex virus. Nature 206, 1374-1375.[CrossRef]
    [Google Scholar]
  35. Sandri-Goldin, R. M. & Mendoza, G. E. ( 1992; ). A herpes simplex virus regulatory protein appears to act posttranscriptionally by affecting mRNA processing. Genes & Development 6, 848-863.[CrossRef]
    [Google Scholar]
  36. Schek, N. & Bachemheimer, S. L. ( 1985; ). Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells. Journal of Virology 55, 601-610.
    [Google Scholar]
  37. Schmelter, J., Knez, J., Smiley, J. R. & Capone, J. P. ( 1996; ). Identification and characterization of a small modular domain in the herpes simplex virus host shutoff protein sufficient for interaction with VP16. Journal of Virology 70, 2124-2131.
    [Google Scholar]
  38. Smibert, C. A., Johnson, D. C. & Smiley, J. R. ( 1992; ). Identification and characterization of the virion-induced host shutoff product of herpes simplex virus gene UL41. Journal of General Virology 73, 467-470.[CrossRef]
    [Google Scholar]
  39. Stoll, G. & Jander, S. ( 1999; ). The role of microglia and macrophages in the pathophysiology of the CNS. Progress in Neurobiology 58, 233-247.[CrossRef]
    [Google Scholar]
  40. Strelow, L. I. & Leib, D. A. ( 1995; ). Role of the virion host shutoff (vhs) of herpes simplex virus type 1 in latency and pathogenesis. Journal of Virology 69, 6779-6786.
    [Google Scholar]
  41. Strom, T. & Frenkel, N. ( 1987; ). Effects of herpes simplex virus on mRNA stability. Journal of Virology 61, 2198-2207.
    [Google Scholar]
  42. Suzutani, T., Machida, H., Sakuma, T. & Azuma, M. ( 1988; ). Effects of various nucleosides on antiviral activity and metabolism of 1-β-d-arabinofuranosyl-E-5-(2-bromovinyl)uracil against herpes simplex virus types 1 and 2. Antimicrobial Agents and Chemotherapy 32, 1547-1551.[CrossRef]
    [Google Scholar]
  43. Suzutani, T., Koyano, S., Takada, M., Yoshida, I. & Azuma, M. ( 1995; ). Analysis of the relationship between cellular thymidine kinase activity and virulence of thymidine kinase-negative herpes simplex virus types 1 and 2. Microbiology and Immunology 39, 787-794.[CrossRef]
    [Google Scholar]
  44. Sydiskis, R. J. & Roizman, B. ( 1966; ). Polysomes and protein synthesis in cells infected with a DNA virus. Science 153, 76-78.[CrossRef]
    [Google Scholar]
  45. Tomazin, R., Hill, A. B., Jugovic, P., York, I., Van Endert, P., Ploegh, H. L., Andrews, D. W. & Johnson, D. C. ( 1996; ). Stable binding of the herpes simplex virus ICP47 protein to the peptide binding site of TAP. EMBO Journal 15, 3256-3266.
    [Google Scholar]
  46. Van Strijp, J. A. G., Van Kessel, K. P. M., Miltenburg, L. A. M., Fluit, A. C. & Verhoef, J. ( 1988; ). Attachment of human polymorphonuclear leukocytes to herpes simplex virus-infected fibroblasts mediated by antibody-independent complement activation. Journal of Virology 62, 847-850.
    [Google Scholar]
  47. Walker, J. & Leib, D. A. ( 1998; ). Protection from primary infection and establishment of latency by vaccination with a herpes simplex virus type 1 recombinant deficient in the virion host shutoff (vhs) function. Vaccine 16, 1-5.[CrossRef]
    [Google Scholar]
  48. Walker, J., Laycock, K. A., Pepose, J. S. & Leib, D. A. ( 1998; ). Postexposure vaccination with a virion host shutoff defective mutant reduces UV-B radiation-induced ocular herpes simplex virus shedding in mice. Vaccine 16, 6-8.[CrossRef]
    [Google Scholar]
  49. York, I. A., Roop, C., Andrews, D. W., Riddell, S. R., Graham, F. L. & Johnson, D. C. ( 1994; ). A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77, 525-535.[CrossRef]
    [Google Scholar]
  50. Zelus, B. D., Stewart, R. S. & Ross, J. ( 1996; ). The virion host shutoff protein of herpes simplex virus type 1: messenger ribonucleolytic activity in vitro. Journal of Virology 70, 2411-2419.
    [Google Scholar]
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